Reaction #8844

Reaction equation

lithium diisopropylamide mono(tetrahydrofuran)

methyl 4-(1-(tert-butoxycarbonyl)-4-(methoxycarbonyl)piperidin-4-yl)butanoate

Methyl 4-(1-(tert-butoxycarbonyl)-4-(methoxycarbonyl)piperidin-4-yl)butanoate

lithium diisopropylamide mono(tetrahydrofuran)

ammonium chloride

ethyl acetate

→

title compound

Yield 110.2%

tert-Butyl 2-(methoxycarbonyl)-1-oxo-8-azaspiro[4.5]decane-8-carboxylate

Yield 110.2%

Solvents

tetrahydrofuran

—

hexanes

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction mixture was stirred for 20 min
2. 2
   Extractionextracted three times with diethyl ether
3. 3
   Washwashed with brine
4. 4
   Dryingdried over sodium sulfate
5. 5
   Concentrationconcentrated

Procedure

To a solution of methyl 4-(1-(tert-butoxycarbonyl)-4-(methoxycarbonyl)piperidin-4-yl)butanoate (20.1 g, 0.058 mol) from Step E in tetrahydrofuran (600 mL) at −78° C. was added lithium diisopropylamide mono(tetrahydrofuran) (47 mL, 0.070 mol, 1.5M solution in cyclohexanes). The reaction mixture was stirred at −78° C. for 25 min. Thin layer chromatography (tlc) analysis (50% ethyl acetate in hexanes) showed that starting material remained. Additional lithium diisopropylamide mono(tetrahydrofuran) (31 mL) was added and the reaction mixture was stirred for 20 min. The reaction mixture was poured into saturated ammonium chloride and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated to afford the title compound (19.9 g) which was taken on to the next step without further purification.

Source